CSF-1 signals directly to renal tubular epithelial cells to mediate repair in mice

J Clin Invest. 2009 Aug;119(8):2330-42. doi: 10.1172/JCI39087. Epub 2009 Jul 1.


Tubular damage following ischemic renal injury is often reversible, and tubular epithelial cell (TEC) proliferation is a hallmark of tubular repair. Macrophages have been implicated in tissue repair, and CSF-1, the principal macrophage growth factor, is expressed by TECs. We therefore tested the hypothesis that CSF-1 is central to tubular repair using an acute renal injury and repair model, ischemia/reperfusion (I/R). Mice injected with CSF-1 following I/R exhibited hastened healing, as evidenced by decreased tubular pathology, reduced fibrosis, and improved renal function. Notably, CSF-1 treatment increased TEC proliferation and reduced TEC apoptosis. Moreover, administration of a CSF-1 receptor-specific (CSF-1R-specific) antibody after I/R increased tubular pathology and fibrosis, suppressed TEC proliferation, and heightened TEC apoptosis. To determine the contribution of macrophages to CSF-1-dependent renal repair, we assessed the effect of CSF-1 on I/R in mice in which CD11b+ cells were genetically ablated and determined that macrophages only partially accounted for CSF-1-dependent tubular repair. We found that TECs expressed the CSF-1R and that this receptor was upregulated and coexpressed with CSF-1 in TECs following renal injury in mice and humans. Furthermore, signaling via the CSF-1R stimulated proliferation and reduced apoptosis in human and mouse TECs. Taken together, these data suggest that CSF-1 mediates renal repair by both a macrophage-dependent mechanism and direct autocrine/paracrine action on TECs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Epithelial Cells / physiology
  • Fibrosis
  • Humans
  • Kidney Tubules / pathology
  • Kidney Tubules / physiology*
  • Macrophage Colony-Stimulating Factor / genetics
  • Macrophage Colony-Stimulating Factor / physiology*
  • Macrophages / physiology
  • Mice
  • Mice, Inbred C3H
  • Receptor, Macrophage Colony-Stimulating Factor / genetics
  • Regeneration
  • Reperfusion Injury / pathology
  • Reperfusion Injury / physiopathology*


  • Macrophage Colony-Stimulating Factor
  • Receptor, Macrophage Colony-Stimulating Factor